Does Chocolate Intake During Pregnancy Reduce the Risks of

Preeclampsia and Gestational Hypertension?

AUDREY F. SAFTLAS, PHD, MPH, ELIZABETH W. TRICHE, PHD, HIND BEYDOUN, PHD, MPH,
AND MICHAEL B. BRACKEN, PHD, MPH

PURPOSE: Chocolate consumption is associated with favorable levels of blood pressure and other cardiovascular disease risk markers. We analyzed a prospective cohort study to determine whether regular chocolate intake during pregnancy is associated with reduced risks of preeclampsia and gestational hypertension
(GH).
METHODS: Subjects were recruited from 13 prenatal care practices in Connecticut (19881991). Inperson interviews were administered at !16 weeks gestation to ascertain risk factors for adverse pregnancy
outcomes. Hospital delivery and prenatal records were abstracted to classify preeclampsia (n Z 58), GH
(n Z 158), and normotensive pregnancies (n Z 2351). Chocolate consumption (servings/week) during
the first and third trimesters was ascertained at initial interview and immediately postpartum, respectively.
Consumers of less than 1 serving/week comprised the referent group. Adjusted odds ratios (aORs) were
estimated by the use of logistic regression.
RESULTS: Chocolate intake was more frequent among normotensive (80.7%) than preeclamptic
(62.5%) or GH women (75.8%), and associated with reduced odds of preeclampsia (first trimester: aOR,
0.55; 95% confidence interval [95% CI], 0.320.95; third trimester: aOR, 0.56; 95% CI, 0.320.97).
Only first trimester intake was associated with reduced odds of GH (aOR,0.65; 95% CI, 0.450.87).
CONCLUSIONS: These findings provide additional evidence of the benefits of chocolate. Prospective
studies are needed to confirm and delineate protective effects of chocolate intake on risk of preeclampsia.
Ann Epidemiol 2010;20:584591. 2010 Elsevier Inc. All rights reserved.
KEY WORDS:

Chocolate, Gestational Hypertension, Preeclampsia, Pregnancy.

INTRODUCTION
It is increasingly recognized that the pathophysiology of
preeclampsia, a leading cause of infant and maternal
morbidity and mortality worldwide, involves many of the
same vascular and metabolic characteristics and risk factors
for cardiovascular disease. Furthermore, accumulating
evidence from long-term follow-up studies indicates that
women with a history of preeclampsia face an increased
risk of developing chronic hypertension, insulin resistance,
and lipid abnormalities later in life (13). Large-scale clinical trials aimed at preventing preeclampsia in high-risk
women have variously focused on antenatal administration
From the Department of Epidemiology, University of Iowa College of
Public Health, Iowa City (A.F.S., H.B.); and Center for Perinatal, Pediatric, and Environmental Epidemiology, Department of Epidemiology
and Public Health, Yale University School of Medicine, New Haven, CT
(E.W.T., M.B.B.).
Address correspondence to: Michael B. Bracken, PhD, MPH, Center for
Perinatal Pediatric and Environmental Epidemiology, Yale University
Schools of Public Health and Medicine, 1 Church Street, 6th Floor, New
Haven, CT 06510. Tel.: 203 764-9375; Fax: 203 764-9378. E-mail:
michael.bracken@yale.edu.
Supported by National Institutes of Health Grants HD32579, AI41040
and DA05484.
Received March 8, 2010; accepted May 10, 2010.
2010 Elsevier Inc. All rights reserved.
360 Park Avenue South, New York, NY 10010

of low-dose aspirin, calcium supplementation, and vitamins

C and E, although none have proven effective (47).
Recent studies indicate that regular intake of chocolate,
particularly dark chocolate, has beneficial effects on cardiovascular disease risk by lowering blood pressure, insulin resistance, serum triglycerides, vascular reactivity, endothelial
dysfunction, oxidative stress, indicators of inflammation,
and antiplatelet activity (8). Each of these physiologic
features has been observed in preeclampsia, providing strong
rationale to test for a protective effect of chocolate intake on
risk of preeclampsia. To date, two published studies in which
the authors used theobromine as a biomarker of chocolate
intake have tested this hypothesis but reported conflicting
findings (9, 10). Triche et al. (10) reported that regular
chocolate consumption and greater levels of theobromine
in cord blood have a protective effect against preeclampsia.
In contrast, Klebanoff and colleagues (9) found no protective effect of increased theobromine in maternal serum
collected after 26 weeks, but did not assess dietary chocolate
consumption.
By using data from the Yale Health in Pregnancy Study,
we addressed the following questions: (i) Is regular chocolate
consumption during pregnancy associated with a reduced
risk of preeclampsia and gestational hypertension? (ii) Do
1047-2797/$ - see front matter
doi:10.1016/j.annepidem.2010.05.010

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Selected Abbreviations and Acronyms

GH Z gestational hypertension
BMI Z body mass index
aOR Z adjusted odds ratio
95% CI Z 95% confidence intervals

the risks of preeclampsia and gestational hypertension vary

by amount of chocolate consumed? (iii) Is the timing or
pattern of chocolate consumption during the first and third
trimesters of pregnancy associated with the risks of
preeclampsia and gestational hypertension. The present
study adds to the current literature by examining
trimester-specific chocolate intake and considering gestational hypertension (GH) as an additional outcome in
a large cohort study of expectant women.

MATERIALS AND METHODS

We conducted an ancillary study within the Yale Health in
Pregnancy Study cohort to identify risk factors for
preeclampsia, which required detailed reviews of all prenatal
and medical records belonging to subjects who were noted to
have evidence of high blood pressure in the parent study
(11). These studies were approved by the Yale University
Human Investigation Committee.
Study Design and Population
The Yale Health in Pregnancy Study is a prospective cohort
study of expectant women who had their first prenatal visit
between April 5, 1988, and December 31, 1991, and
planned to deliver at the Yale-New Haven Hospital. The
study was originally designed to assess the influence of environmental tobacco smoke exposure on fetal growth and
preterm delivery. Details of study methods have been
described previously (11, 12). Subjects were recruited from
11 private obstetric practices and two health maintenance
organizations. Exclusion criteria included diabetes mellitus,
non-English speaking, >16 weeks gestation, or previous
study participation. A total of 3591 women screened eligible
for the initial interview, which had to be completed before
16 weeks gestation. A total of 2967 (83%) women
completed the interview; the remaining subjects either
refused to participate (16%) or could not be reached for
an initial contact (1.4%). The current analysis is restricted
further to subjects who had singleton deliveries and hospital
delivery records available for abstraction by research staff
(96%) to facilitate accurate classification of three outcome
groups: preeclampsia, GH, and normal blood pressure.
The initial study interview was conducted in-person
before 16 weeks gestation by trained interviewers. The
interview was usually conducted at the subjects home and

Saftlas et al.
PREECLAMPSIA AND CHOCOLATE IN PREGNANCY

585

took approximately 1 hour to administer. The interviewers

obtained information on maternal demographics, medical
and reproductive history, height, prepregnancy weight,
antenatal smoking, alcohol, caffeine, and chocolate
consumption, occupational factors, and exercise habits.
Subjects also completed a postpartum interview, usually
conducted in person at the hospital within the first few
days of delivery, to obtain information on exposures during
the seventh, eighth, and ninth gestational months. Study
abstractors were trained to carefully document chart notations of increased blood pressure for all subjects because of
the link between preeclampsia and the parent studys
primary outcomes.
Classification of Hypertension in Pregnancy
To achieve accurate and consistent case definitions of
preeclampsia and GH, we conducted a supplementary
review of all prenatal and hospital delivery records for the
415 (15%) participants who had some indication of elevated
blood pressure during pregnancy based on hospital chart
reviews or in-person interviews. The abstractors recorded
blood pressure readings, urine protein values, laboratory
test results, and other signs and symptoms of preeclampsia.
On the basis of this review, women were assigned to one of
the following categories in accordance with current criteria
from the American College of Obstetricians and Gynecologists: (i) no hypertension (n Z 98); (ii) chronic hypertension (n Z 73); (iii) GH (n Z 158); (iv) preeclampsia
(n Z 58); (v) superimposed preeclampsia (n Z 14); and,
(vi) uncategorized hypertension or unknown hypertension
status (n Z 14). Women with HELLP syndrome (n Z 13)
were coded as superimposed preeclampsia or preeclampsia,
according to the presence or absence of chronic hypertension.
The present analysis includes subjects with a final diagnosis of GH, preeclampsia, or normotensive during pregnancy. GH was defined as systolic blood pressure >140
mmHg or diastolic blood pressure >90 mmHg after 20
weeks gestation on two or more occasions at least 6 hours
apart with no evidence of proteinuria. Preeclampsia was
defined as GH with proteinuria (ie, two or more dipstick
readings of >1 or a 24-hour urine collection of >300mg protein). The comparison group had no indication of
high blood pressure during pregnancy (n Z 2324). All
subjects who underwent chart review because they had
a notation of elevated blood pressure were excluded from
the comparison group, including the 98 with a final classification of no hypertension.
Assessment and Classification of Chocolate Intake
Average weekly consumption of chocolate drinks and foods
was assessed by two questions included on both the initial
interview (covering months 13) and the postpartum

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Saftlas et al.
PREECLAMPSIA AND CHOCOLATE IN PREGNANCY

interview (covering months 79). At the initial interview,

women were asked: (i) Since you became pregnant, have
you been drinking one or more cups of hot chocolate, cocoa,
or chocolate milk per week? and (ii) Since you became
pregnant, have you been eating one or more servings of
chocolate candy, chocolate cake, chocolate cookies or
chocolate ice cream per week? Women who responded
yes were then asked to recall their average weekly intake
of chocolate drinks and/or chocolate foods since becoming
pregnant by using the following close-ended responses:
(i) 13 cups (or servings) a week, (ii) 46 cups (or servings) a week, (iii) 1 cup (or serving) daily, (iv) 2 cups (or
servings) daily, (v) 34 cups (or servings) daily,
(vi) 510 cups (or servings) daily, and (vii) More than
10 cups (or servings) daily. These questions were repeated
at the postpartum interview, referring to months 79. On
the basis of data from the two questions, the combined
number of servings of chocolate drinks and foods consumed
per week was computed separately for the first and third
trimesters, and categorized as follows: (i) No regular chocolate consumption, defined as !1 serving per week (referent
category); (ii) 13 servings per week; and (iii) 4 or more
servings per week. To examine for an effect of the timing
of chocolate intake, a cross-classified variable was created
with the following categories: (i) no regular chocolate intake
during trimesters 1 and 3 (referent group); (ii) regular chocolate intake during trimester 1 only; (iii) intake during
trimester 3 only; and, (iv) intake during both trimesters 1
and 3. Self-reports of chocolate consumption in the third
trimester of pregnancy, using almost identical self-report
questions as used here, is correlated with cord blood theobromine levels (9).
Assessment of Confounding
Established maternal risk and protective factors for
preeclampsia were examined as potential confounders of
the association between chocolate intake and the risks of
preeclampsia and GH. Body mass index (BMI) was examined as a continuous variable and classified into four categories: underweight (!18.5), normal weight (18.524.9),
overweight (25.029.9), and obese (>30.0), per the Institute of Medicine definitions for reproductive-aged women
(13). Maternal age at delivery was analyzed as a continuous
and a categorical variable (!25, 2529, 3034, and 35).
To adjust for parity and abortion history in nulliparous
women, we constructed a cross-classification variable coded
as: (i) nulliparous/no history of spontaneous or induced
abortion, (ii) nulliparous/history of spontaneous or induced
abortion, and (iii) multiparous. Also examined were
maternal education (high school; some college; college
graduate; graduate education); cigarette smoking during
pregnancy (no, yes); race (white, nonwhite); caffeine intake
in the first or seventh month of pregnancy (no caffeine;

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month 1 only; month 7 only; months 1 and 7); fetal gender,

and gestational diabetes during the index pregnancy.
Caffeine consumption, a potentially important confounder,
has been studied previously in this data set (14), and detailed
methods for their measurement previously reported (15).
Statistical Analysis
Univariate, bivariate, and multivariate analyses were performed by the use of the Statistical Analysis Software
(SAS) version 9.1. All tests were two-sided and with an
alpha level of 0.05. Chi-square tests were used to compare
the associations of preeclampsia, GH, and chocolate exposure with potentially confounding variables. Logistic regression was performed to compute crude and adjusted odds
ratios (aORs) and 95% confidence intervals (95% CIs).
Confounding was assessed by examining changes in exposure odds ratios when a covariable was added or removed
from the model; variables that changed the exposure
estimates by at least 10% were retained in the final models.

RESULTS
We analyzed the two sources of chocolate (ie, chocolate foods
and chocolate drinks) and found no difference in the magnitude of their association with PE risk. Therefore, chocolate
consumption from these combined sources was analyzed.
Table 1 shows the frequency distributions of demographic, reproductive, and lifestyle characteristics of the
final analysis population (n Z 2508) categorized by
trimester of chocolate consumption during pregnancy, and
the proportion with preeclampsia (2.4%) and GH (6.4%).
A total of 48% of subjects reported regular weekly intake
of chocolate drinks or foods during both the first and third
trimesters, 10% reported intake during the first trimester
only, 22% reported in the third trimester only, and 20% reported no regular chocolate consumption. Chocolate
consumption was more frequently reported by women who
were younger than 35 years of age, white, had a BMI less
than 25, drank caffeinated beverages, or who did not
develop gestational diabetes during the index pregnancy.
Among the putative risk factors for preeclampsia and
GH, nulliparity and obesity were significantly associated
with both hypertensive disorders (Table 1). Male fetal sex
was significantly associated with increased risk of
preeclampsia but not GH. Although maternal age less
than 30 years was significantly associated with increased
risk of GH, maternal age was not associated with
preeclampsia risk. Although maternal race, education,
smoking during pregnancy, caffeine intake, and gestational
diabetes were not significantly associated with preeclampsia
or GH, rates of preeclampsia were substantially greater
among nonwhite patients and gestational diabetics.

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PREECLAMPSIA AND CHOCOLATE IN PREGNANCY

587

TABLE 1. Distribution of population characteristics by timing of chocolate consumption during pregnancy and by preeclampsia and
gestational hypertension status, Yale Health in Pregnancy Study, 1988 to 1991
Chocolate intake during pregnancy

Overall
Maternal age, yrs
1824
2529
3034
3539
40
Race
White
Nonwhite
Maternal education
High school
Some college
College graduate
Graduate school
Body mass index, kg/m2
!18.5
18.524.9
25.029.9
>30.0
Parity
Nulliparous, no
previous pregnancy
Nulliparous,
with previous pregnancy
Parous
Smoked during pregnancy
No
Yes
Caffeine, month 1 or 7
Neither
Month 1 only
Month 7 only
Months 1 and 7
Fetal sex
Female
Male
Gestational diabetes?
No
Yes

Preeclampsia

No.*

No regular
intake, %

Trimester
1 only, %

Trimester
3 only, %

Trimesters
1 and 3, %

2508

20.0

10.2

22.2

47.6

c
p-value

No.

2382

2.4

0.002
140
693
1069
521
85

18.6
17.0
19.6
23.8
28.2

10.0
10.3
10.7
10.2
4.7

25.7
18.3
23.0
24.0
25.9

45.7
54.4
46.7
42.0
41.2

2287
219

19.2
28.8

9.8
15.1

22.0
24.2

49.2
32.0

450
638
747
673

17.1
19.6
19.4
23.0

13.3
10.3
8.8
9.5

23.6
19.8
23.0
22.6

46.0
50.3
48.7
44.9

76
1753
465
187

25.0
18.3
22.4
26.2

9.2
9.5
10.3
17.1

13.2
22.5
22.8
21.4

52.6
49.7
44.5
35.3

670

20.8

10.0

22.4

439

20.1

10.7

1399

19.7

10.2

Gestational hypertension
2

c
p-value

No.

2482

6.4

138
691
1051
517
85

8.0
8.7
5.0
5.8
5.9

2264
216

6.4
6.5

442
629
739
672

8.1
7.5
5.6
5.1

76
1739
457
180

2.6
5.0
9.2
15.0

0.59

0.03

132
646
1027
495
82

3.8
2.3
2.7
1.6
2.4

2170
210

2.3
3.8

420
598
715
649

3.3
2.7
2.4
1.7

76
1686
428
162

2.6
2.0
3.0
5.6

46.9

614

4.9

648

9.9

23.2

46.0

414

3.1

435

7.8

21.7

48.5

1354

1.1

1399

4.3

2100
359

6.2
7.8

679
319
285
1098

5.0
5.6
8.1
6.9

1246
1206

6.3
6.6

2334
118

6.4
7.6

0.18

!0.0001

0.07

9.8
12.8

22.4
21.0

47.5
48.8

692
330
292
1114

23.0
22.4
19.2
17.3

8.2
13.0
12.3
10.3

25.3
23.9
21.9
19.9

43.5
40.6
46.6
52.4

1249
1232

18.8
21.4

9.3
10.8

23.1
21.3

48.8
46.5

2359
122

18.9
44.3

8.6
37.7

23.0
5.7

49.5
12.3

!0.0001

!0.0001

0.20
20.4
17.4

0.09

0.04

0.97

2139
367

0.94

0.38

0.0005

!0.0001

0.77
2018
340

2.4
2.7

659
312
270
1044

2.1
3.5
3.0
2.1

1186
1165

1.6
3.3

2237
114

2.3
4.4

0.0002

0.25

0.45

0.16

0.23

0.009

0.83

0.16

!0.0001

c2
p-value

0.59

*Totals may vary because of missing data.

Analysis of regular chocolate consumption in the first

and third trimesters (Fig. 1) indicates that preeclamptic
women were less likely to regularly consume chocolate
(37.5%) than normotensive women (19.3%) or those with
GH (24.2%). Nearly one-half (48%) of normotensive
women reported regular chocolate consumption in both
trimesters 1 and 3 versus 35.7% and 40.8% of women with
preeclampsia and GH, respectively. Overall, few subjects reported regular chocolate consumption in the first trimester
only (7.1%10.5%), whereas intake in the third trimester
only was substantially more prevalent (19.6%27.4%).

Analyses of the influence of regular chocolate intake by

number of weekly servings (dose) and trimester of consumption (timing of exposure) on risk of preeclampsia and GH
are summarized in Table 2. Regular consumption of 1 to 3
servings per week during the first trimester was associated
with reduced risk of preeclampsia (aOR, 0.57; 95% CI,
0.301.09); intake of four or more servings per week
conferred a similar level of protection (aOR, 0.52; 95%
CI, 0.241.10). Women who reported any regular chocolate consumption (>13 servings/week) during the first
trimester had a significantly reduced risk of 0.55

588

Saftlas et al.
PREECLAMPSIA AND CHOCOLATE IN PREGNANCY

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FIGURE 1. Distribution of chocolate consumption by hypertension status in pregnancy, Yale Health in Pregnancy Study, 1988 to 1991.

(0.320.95), the same as that observed among those with

any regular consumption during trimester 3 (aOR, 0.56;
95% CI, 0.320.97).
Analysis of the cross-classification variable of regular
chocolate intake (no, yes) by trimester of exposure further
substantiated that any regular chocolate intake is associated
with significantly reduced risk of preeclampsia relative to
women who reported no regular chocolate consumption
in both trimesters 1 and 3: aOR estimates were 0.31
(0.100.93) for trimester 1 consumption only, 0.44
(0.200.94) for trimester 3 consumption only, and 0.41
(0.210.77) for consumption during both trimesters.
Regular chocolate intake was also associated with a reduced
risk of GH but only among subjects who reported first
trimester consumption (aOR, 0.64; 0.460.90); consumption
in the third trimester only was not associated with reduced risk
(aOR, 0.98). Although regular first trimester consumption of
1 to 3 servings per week was protective against GH (aOR,
0.54; 95% CI, 0.360.92), a higher intake of four or more
servings per week did not confer further protection (aOR,
0.80; 95% CI, 0.531.21). Analysis of regular chocolate
consumption by trimester of intake also suggests that first
trimester consumption alone (aOR, 0.52; 95% CI,
0.261.04) but not third trimester consumption alone
(aOR, 1.04; 95% CI, 0.651.66) is protective against GH.
DISCUSSION
Women who reported regular chocolate consumption of >1
to 3 servings/week had a 50% or greater reduced risk of

preeclampsia, which did not appear to be dose dependent.

Analysis by timing of exposure suggested that regular
chocolate intake during the first or third trimester was
equally protective against preeclampsia. The greatest rate
of preeclampsia (4.5%) occurred among women who did
not regularly consume chocolate in the first and third
trimesters of pregnancy. In contrast, only women who regularly consumed chocolate during the first trimester had
a reduced risk of GH.
Given our current understanding of the pathophysiology
of preeclampsia as a 2-stage disease process, it is biologically plausible that trimesters 1 and 3 would be critical
windows for exposure and possible intervention. Defective
placentation of preeclampsia is initiated in the first trimester
of pregnancy (16, 17). The resulting placental oxidative
stress and inflammation is hypothesized to trigger the release
of proinflammatory syncytiotrophoblast-derived factors (eg,
sFlt-1), which lead to maternal systemic vascular endothelial disruption and the eventual clinical manifestation of
preeclampsia in the third trimester of pregnancy (16).
Triche et al. (10) also found that self-reported, regular
consumption in the third trimester was protective against
preeclampsia; however, they did not find a protective effect
of first trimester consumption. Our findings are also consistent with their report of a 60% reduction in preeclampsia
associated with levels of cord blood theobromine at or above
the second quartile of exposure (9). In contrast, our findings
are not consistent with those of Klebanoff et al. (9), who
found no protective effect of theobromine measured in
maternal serum after the 26th week of gestation for

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PREECLAMPSIA AND CHOCOLATE IN PREGNANCY

589

TABLE 2. Crude and adjusted ORs and 95% CIs for associations between chocolate consumption variables and risk of preeclampsia and
gestational hypertension, Yale Health in Pregnancy Study, 1988 to 1991
Preeclampsia
Chocolate consumption,
variable*
Chocolate, first trimester
No regular consumptionz
13 servings/wk
4 servings/wk
Chocolate, first trimester
No regular consumptionz
1 servings/wk
Chocolate, third trimester
No regular consumptionz
13 servings/wk
4 servings/wk
Chocolate, third trimester
No regular consumptionz
>13 servings/wk
Chocolate, first or
third trimester
Neither trimesterz
Trimester 1 only
Trimester 3 only
Trimesters 1 and 3

Gestational hypertension

Crude
OR

95%
CI

Adjusted
ORy

95%
CI

986 3.4
799 1.9
591 1.5

1.00
0.54
0.47

(0.291.02)
(0.221.00)

1.00
0.57
0.52

(0.301.09)
(0.241.10)

986 3.4
1390 1.7

1.00
0.51

(0.300.87)

711 3.7
843 1.8
803 2.0

1.00
0.46
0.51

711 3.7
1646 1.9

464
244
513
1130

No.

4.5
1.6
2.1
1.8

Crude
OR

95%
CI

Adjusted
ORy

95%
CI

1034 7.8
822 4.6
621 6.3

1.00
0.53
0.74

(0.350.80)
(0.501.10)

1.00
0.54
0.80

(0.360.82)
(0.531.21)

1.00
0.55

1034 7.8
(0.320.95) 1443 5.3

1.00
0.62

(0.450.87)

1.00
0.64

(0.460.90)

(0.240.89)
(0.270.97)

1.00
0.54
0.57

(0.281.07)
(0.291.10)

735 6.8
877 5.6
845 6.9

1.00
0.82
0.90

(0.551.24)
(0.601.35)

1.00
0.96
1.00

(0.631.46)
(0.661.51)

1.00
0.48

(0.280.83)

1.00
0.56

735 6.8
(0.320.97) 1722 6.2

1.00
0.86

(0.601.22)

1.00
0.98

(0.681.41)

1.00
0.35
0.41
0.35

(0.121.02)
(0.190.89)
(0.190.66)

1.00
0.31
0.44
0.41

481
(0.100.93) 252
(0.200.94) 545
(0.210.77) 1174

1.00
0.59
0.99
0.62

(0.301.16)
(0.621.56)
(0.410.95)

1.00
0.52
1.04
0.69

(0.261.04)
(0.651.66)
(0.451.07)

No.

7.9
4.8
7.9
5.5

95% CI Z 95% confidence interval; OR Z odds ratio.

*Separate logistic models were run for each of the five chocolate consumption variables.
y
Adjusted for body mass index and parity/abortion.
z
No regular consumption Z consuming !1 serving of chocolate food or drink per week during the first or third trimester.

preeclampsia. They also reported that preeclampsia risk

increased in a doseresponse fashion with increasing levels
of theobromine measured in maternal serum collected
before 20 weeks gestation. Possible explanations for the
disparate findings include the very different study populations; differences in the length of storage of the serum specimens; different definitions of preeclampsia; and differences
in the possible sources of theobromine during the 40-year
period separating these studies.
Although Triche et al. (10) found evidence of an inverse
doseresponse relationship of theobromine levels in cord
serum with preeclampsia risk, our questionnaire assessment
of dietary chocolate intake was not adequately robust to
detect a doseresponse effect. Different chocolate products
and sources contain varying amounts of cocoa; such heterogeneity in cocoa content makes it very difficult to assess for
doseresponse relationships with the use of food frequency
questionnaires. This problem is not an unusual one in epidemiology; even in a recent study of the association of vitamin
D intake with risk of preeclampsia, no association was
observed based on food frequency dietary measurements of
vitamin D intake; however, a 27% reduced risk of
preeclampsia was detected when analyses were restricted
to assessments of vitamin D intake from supplements alone
(1015 mg/d vs. no supplementation) (18).

There is considerable pathophysiologic and epidemiologic support for our findings from literature examining
the cardiovascular effects of chocolate intake in adult populations. A recent review reported findings from 11 human
studies of direct, beneficial effects of cocoa exposure on
endothelial function, including improvements in vasodilation, coronary circulation, nitric oxide levels, blood pressure, and platelet function (8). Endothelial dysfunction is
implicated as a central feature in the pathogenesis of
preeclampsia. A recent 16-year epidemiologic follow-up
study of post-menopausal participants in the Iowa Womens
Health Study revealed chocolate intake was associated with
reduced rates of cardiovascular disease mortality (19).
The authors of a recent systematic review of 10 randomized controlled trials assessed the antihypertensive effects of
flavinol-rich cocoa reported significant decreases in systolic
(4.5 mmHg) and diastolic (2.5 mmHg) blood pressure
(20). Most of the reviewed trials used relatively high doses
of cocoa for periods of 2 to 18 weeks. The authors of one trial
examined very low doses of dark chocolate (6.3 g/d) during
the course of 18 weeks but still found highly significant
reductions in blood pressure (2.9 mmHg systolic and
1.9 mmHg diastolic) (21). Two new trials of low-dose
chocolate intake report similar drops in systolic and diastolic
blood pressure (22, 23). Desch et al. (20) compared low-dose

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PREECLAMPSIA AND CHOCOLATE IN PREGNANCY

(6 g/d) versus high dose (25 g/d) intakes during the course of
3 months but found no difference in blood pressure changes
between the two groups (20). In an adult German population, significant reductions in blood pressure were also
observed with low-dose consumption (6 g/d), with a larger
reduced risk for myocardial infarction and stroke (22).
The difference between a small effect on blood pressure
and a larger clinical effect may result from the influence of
cocoa on other cardiovascular risk factors, particularly those
influencing inflammation. A diet of 6.7 g/d of dark chocolate
has been associated with decreased serum C-reactive
proteins, a marker of inflammation (24).
Several recent studies conducted in various patient populations suggest there are sustained benefits in vascular function after a single dose intake of flavanol-rich cocoa (25, 26).
A recent study of oral intake of cocoa found that the highest
plasma levels of flavanols peak 2 to 3 hours after ingestiond
but are still measurable 8 hours after ingestion (27, 28).
There are several strengths of the current study analysis.
Data are derived from a large cohort of women interviewed
early in pregnancy for risk factors relating to adverse
pregnancy outcomes. First-trimester exposure data were obtained prospectively with respect to the outcomes. Furthermore, recall bias is unlikely to influence third-trimester
exposure self-reports because chocolate was not recognized
as having antihypertensive properties during the study
period (19881991). Classification of preeclampsia and
GH was determined on the basis of abstraction of blood pressure and urinary protein readings from both prenatal and
hospital delivery chart data, and strict research definitions
were uniformly applied to reduce misclassification and
increase specificity of case diagnoses. We were also able to
consider timing of regular chocolate intake during pregnancy, and had extensive data on a number of potentially
confounding variables. The study used both self-report and
medical chart data in the assessment of exposure, outcome,
and confounding variables. In addition, we are first to
examine the association between chocolate consumption
and risk of GH.
There are some limitations of the current research. The
self-reported exposure data may have led to misclassification
as it is very difficult to accurately quantify serving sizes and
cocoa content of different products. In addition, our questionnaire did not differentiate between dark and other types
of chocolate. Because the data were collected prospectively
with respect to the outcome, we would expect that the
misclassification would be nondifferential and lead to attenuation of risk estimates. Our study would have been
enhanced by having biomarker data (eg, theobromine) to
validate associations between self-reported chocolate
consumption and risk of preeclampsia and GH.
As we did not assess other dietary constituents other than
caffeinated beverages, it is possible that our results are

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August 2010: 584591

subject to unmeasured confounding. Although there are

very few well-established risk factors for preeclampsia, we
have controlled for many of these. To date, there are no dietary factors that have been consistently associated with
preeclampsia, providing support that our study findings
would be unlikely to change with additional information
about diet during pregnancy (29).
Another potential bias is that overweight women may
underreport their chocolate intake. We re-ran the analyses,
restricted to women with normal prepregnancy BMI, to
address this potential bias and found nearly identical risk
estimates as those for all women. Similarly, to address the
possibility of residual confounding by smoking during pregnancy, which has been associated with a reduced risk of
preeclampsia, we re-ran the final models among only nonsmokers and found no change in the risk estimates.
We also considered the possibility of reverse causality
whereby women who developed high blood pressure might
be less likely to consume chocolate after diagnosis.
However, we excluded from analysis women who had
elevated blood pressure before 20 weeks gestation. Furthermore, the protective influence of regular chocolate
consumption was apparent with first-trimester exposure,
which, by definition, preceded all diagnoses of preeclampsia,
GH, or high blood pressure readings in this study population. We also noted that women with gestational diabetes
reported reduced chocolate consumption, particularly later
in pregnancy. There was no evidence, however, that gestational diabetes was a confounder of the association of chocolate consumption and risk of either hypertensive outcome.
Further, when models were restricted to nondiabetic
women, no changes in risk estimates were noted.
In conclusion, these findings provide additional evidence
of the potential benefits of chocolate consumption. Prospective studies are needed to confirm and delineate protective
effects of chocolate intake on risk of preeclampsia. Such
studies require detailed assessments of dietary chocolate
intake and its metabolites during the course of pregnancy.

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